Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes.

Abstract

Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has remained unresolved. Here we used concurrent transcriptome-wide identification of NMD substrates and their 5'-3' decay intermediates to establish that SMG6-catalyzed endonucleolysis widely initiates the degradation of human nonsense RNAs, whereas decapping is used to a lesser extent. We also show that a large proportion of genes hosting snoRNAs in their introns produce considerable amounts of NMD-sensitive splice variants, indicating that these RNAs are merely by-products of a primary snoRNA production process. Additionally, transcripts from genes encoding multiple snoRNAs often yield alternative transcript isoforms that allow for differential expression of individual coencoded snoRNAs. Based on our findings, we hypothesize that snoRNA host genes need to be highly transcribed to accommodate high levels of snoRNA production and that the expression of individual snoRNAs and their cognate spliced RNA can be uncoupled via alternative splicing and NMD.

DOI: 10.1101/gad.246538.114
020406080201520162017
Citations per Year

115 Citations

Semantic Scholar estimates that this publication has 115 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{LykkeAndersen2014HumanNR, title={Human nonsense-mediated RNA decay initiates widely by endonucleolysis and targets snoRNA host genes.}, author={S\oren Lykke-Andersen and Yun Chen and Britt R Ardal and Berit Lilje and Johannes Waage and Albin Sandelin and Torben Heick Jensen}, journal={Genes & development}, year={2014}, volume={28 22}, pages={2498-517} }